Theodore C. Jessop

Bio: Theodore C. Jessop is an academic researcher from Stanford University. The author has contributed to research in topics: Membrane potential & Lipid bilayer. The author has an hindex of 7, co-authored 14 publications receiving 2431 citations.

Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into Mammalian cells.

Abstract: The interactions between various functionalized carbon nanotubes and several types of human cancer cells are explored. We have prepared modified nanotubes and have shown that these can be derivatized in a way that enables attachment of small molecules and of proteins, the latter through a novel noncovalent association. The functionalized carbon nanotubes enter nonadherent human cancer cells as well as adherent cell lines (CHO and 3T3) and by themselves are not toxic. While the fluoresceinated protein streptavidin (MW approximately 60 kD) by itself does not enter cells, it readily enters cells when complexed to a nanotube-biotin transporter and exhibits dose-dependent cytotoxicity. The uptake pathway is consistent with adsorption-mediated endocytosis. The use of carbon nanotubes as molecular transporters could be exploited for various cargos. The biocompatibility and unique physical, electrical, optical, and mechanical properties of nanotubes provide the basis for new classes of materials for drug, protein, and gene delivery applications.

Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells.

Abstract: The results described herein support a mechanistic hypothesis for how guanidine-rich transporters attached to small cargos (MW ca. 95%) into the octanol layer. In contrast, ornithine oligomers partition almost exclusively into the water layer with and without added sodium laurate. The different partitioning between guanidinium-rich and ammonium-rich oligomers in the presence of sodium laurate is consistent with the ability of the former to form a bidentate hydrogen bonded ion pair. Mono- and dimethylated arginine oligomers, which like ornithine can only efficiently form monodentate hydrogen bonds, were prepar...

Oligocarbamate molecular transporters: design, synthesis, and biological evaluation of a new class of transporters for drug delivery.

Abstract: Molecular transporters have the ability to deliver drugs and probe molecules into cells and tissues irrespective of their physical properties. We now report the design, synthesis, and biological evaluation of a new family of molecular transporters, guanidinylated oligocarbamates that enable exceptionally efficient uptake into cells and tissues. The synthesis features a solid-phase stepwise oligomerization to obtain the oligocarbamates and a single step perguanidinylation for the facile introduction of up to nine guanidinium groups. The oligocarbamate 9-mer is found to be among the most efficient transporters known, entering cells faster than even d-Arg9 and HIV-1 Tat49-57. Significantly, this new family of transporters also enables uptake into the formidable skin barrier of a probe molecule that by itself does not penetrate skin.

Guanidinium transport reagents and conjugates

Abstract: Transport reagents and conjugates of therapeutic agents linked to transport reagents are described. In particular, the transport reagents have a plurality of guanidinium moieties that are either contiguous or spaced along a backbone, but are sufficiently removed from the backbone via tethers, to allow their interaction with a cell or tissue surface, leading to uptake of the therapeutic agent.

Recent advances with liposomes as pharmaceutical carriers.

Abstract: Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.

Chemistry of Carbon Nanotubes

Abstract: Department of Materials Science, University of Patras, 26504 Rio Patras, Greece, Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vass. Constantinou Avenue, 116 35 Athens, Greece, Institut de Biologie Moleculaire et Cellulaire, UPR9021 CNRS, Immunologie et Chimie Therapeutiques, 67084 Strasbourg, France, and Dipartimento di Scienze Farmaceutiche, Universita di Trieste, Piazzale Europa 1, 34127 Trieste, Italy

PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs

Abstract: It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO−PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via π−π stacking. The resulting NGO−PEG−SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO−PEG−SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.

PEGylated Nano-Graphene Oxide for Delivery of Water Insoluble Cancer Drugs

Abstract: It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nano-graphene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analog, SN38 non-covalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.

Cytotoxicity of Nanoparticles

Abstract: Human exposure to nanoparticles is inevitable as nanoparticles become more widely used and, as a result, nanotoxicology research is now gaining attention. However, while the number of nanoparticle types and applications continues to increase, studies to characterize their effects after exposure and to address their potential toxicity are few in comparison. In the medical field in particular, nanoparticles are being utilized in diagnostic and therapeutic tools to better understand, detect, and treat human diseases. Exposure to nanoparticles for medical purposes involves intentional contact or administration; therefore, understanding the properties of nanoparticles and their effect on the body is crucial before clinical use can occur. This Review presents a summary of the in vitro cytotoxicity data currently available on three classes of nanoparticles. With each of these nanoparticles, different data has been published about their cytotoxicity due to varying experimental conditions as well as differing nanoparticle physiochemical properties. For nanoparticles to move into the clinical arena, it is important that nanotoxicology research uncovers and understands how these multiple factors influence the toxicity of nanoparticles so that their undesirable properties can be avoided.